Neurotransmitter evaluation in the hippocampus of rats after intracerebral injection of TsTX scorpion toxin

TsTX is an á-type sodium channel toxin that stimulates the discharge of neurotransmitters from neurons. In the present study we investigated which neurotransmitters are released in the hippocampus after TsTX injection and if they are responsible for electrographic or histopathological effects. Microdialysis revealed that the toxin increased glutamate extracellular levels in the hippocampus; however, levels of gamma-aminobutyric acid (GABA), glycine, 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were not significantly altered. Neurodegeneration in pyramidal cells of hippocampus and electroencephalographic alterations caused by the toxin were blocked by pretreatment with riluzole, a glutamate release inhibitor. The present results suggest a specific activity of TsTX in the hippocampus which affects only glutamate release.

Embriotoxic effects of maternal exposure to Tityus serrulatus scorpion venom

Tityus serrulatus is the most venomous scorpion in Brazil; however, it is not known whether its venom causes any harm to the offspring whose mothers have received it. This study investigates whether the venom of T. serrulatus may lead to deleterious effects in the offspring, when once administered to pregnant rats at a dose that causes moderate envenomation (3mg/kg). The venom effects were studied on the 5th and on the 10th gestation day (GD5 and GD10). The maternal reproductive parameters of the group that received the venom on GD5 showed no alteration. The group that received the venom on GD10 presented an increase in post-implantation losses. In this group, an increase in the liver weight was also observed and one-third of the fetuses presented incomplete ossification of skull bones. None of the groups that received the venom had any visceral malformation or delay in the fetal development of their offspring. The histopathological analysis revealed not only placentas and lungs but also hearts, livers and kidneys in perfect state. Even having caused little effect on the dams, the venom may act in a more incisive way on the offspring, whether by stress generation or by a direct action.

Haloperidol treatments increased macrophage activity in male and female rats: influence of corticosterone and prolactin serum levels.

Haloperidol is a receptor D2 antagonist frequently used in the treatment of schizophrenic patients. Haloperidol increased prolactin release from anterior pituitary gland, and prolactin modulates immune system activity. Groups of six male and female rats received an acute 2 mg/kg haloperidol treatment (E1), or a long-term (E2) haloperidol treatments (2 mg/kg/day for 21 days); control rats were treated similarly, but with control solution (groups C1 and C2, respectively). In this work long-term haloperidol treatment (E2) increased macrophage spreading, phagocytosis and NO release in male and female rats. However, acute haloperidol treatment (E1) did not change macrophage activity. Corticosterone and prolactin serum levels were increased after acute (E1) and long-term (E2) haloperidol treatments in male and female rats, being this increment higher in female. Macrophage of male and female rats presented the same pattern of alterations after acute and long-term haloperidol treatments. Haloperidol-induced macrophage activation was discussed in the light of a possible indirect effect through prolactin increments in rats, or, alternatively, as a consequence of a direct action of macrophage dopamine receptor.

Haloperidol treatments increased macrophage activity in male and female rats: Influence of corticosterone and prolactin serum levels

Haloperidol is a receptor D2 antagonist frequently used in the treatment of schizophrenic patients. Haloperidol increased prolactin release from anterior pituitary gland, and prolactin modulates immune system activity. Groups of six male and female rats received an acute 2 mg/kg haloperidol treatment (E1), or a long-term (E2) haloperidol treatments (2 mg/kg/day for 21 days); control rats were treated similarly, but with control solution (groups C1 and C2, respectively). In this work long-term haloperidol treatment (E2) increased macrophage spreading, phagocytosis and NO release in male and female rats. However, acute haloperidol treatment (E1) did not change macrophage activity. Corticosterone and prolactin serum levels were increased after acute (E1) and long-term (E2) haloperidol treatments in male and female rats, being this increment higher in female. Macrophage of male and female rats presented the same pattern of alterations after acute and long-term haloperidol treatments. Haloperidol-induced macrophage activation was discussed in the light of a possible indirect effect through prolactin increments in rats, or, alternatively, as a consequence of a direct action of macrophage dopamine receptor.

Effects of scorpion Tityus serrulatus venom toxin TS-8F on rat learning and memory

Scorpion venom neurotoxins are responsible for toxicity and pharmacological effects. They are active in sodium and potassium channels leading to an increase in the release of neurotransmitters, such as glutamate. Glutamate is found in large quantities in the hippocampus (HPC) and is involved in the long-term potentiation (LTP) induction. The HPC is known to be related to certain kinds of memory. The aim of this study is to evaluate the effects of Tityus serrulatus TS-8F toxin on rat behavior with emphasis on learning and memory. We analyzed the effects of different doses of TS-8F on rat behavior in home cages, open-field (habituation), inhibitory avoidance, T-maze, and hippocampus morphology. In the first two experiments, 0.05µg/animal dose of TS-8F did not cause convulsion but led to a decrease in locomotion (LO) frequency in the open-field first session. During the second session, rats receiving 0.03µg/animal TS-8F showed a decrease in LO and rearing frequency (RE); controls only showed decreased LO; and those receiving 0.05µg/animal showed no significant changes. In inhibitory avoidance, T-maze, and HPC morphology experiments no significant differences were observed. It is concluded that TS-8F may exert some influence in rat learning and memory and seems to be useful as a pharmacological tool. Further research is required to elucidate all possible uses of this toxin.

Convulsive effects of some isolated venom fractions of the Tityus serrulatus scorpion: behavioral, electroencephalographic, and neuropathological aspects

It has been previously shown that the crude venom of Tityus serrulatus can cause convulsions. This study was designed to investigate the neurotoxic effects of B, C, G, and K fractions isolated from this venom. Intravenous injection of these fractions in mice (0.6 - 6.0 mg/kg body weight) showed that the C fraction is a potent convulsant and G fraction decreased the threshold for tonic hand limb extension elicited by transauricular electroshock. Unilateral injection of B, C, and K fractions, but not G fraction, into the spikes and epileptic discharges that began in the hippocampus and evolved to the cortex. The following motor signs were observed: movements of facial muscles, wet dog shake, immobility, myoclonus, wild-running with clonus, and in some cases, loss of postural control. Intrahippocampal injection of B, C, and K fraction, but not G fraction, caused neuronal loss at the injection site as well as in other hippocampal areas. The effect of these fractions on epileptiform activity and on neuronal loss was dose-dependent. The severity of the epileptiform activity in the ipsilateral hippocampus correlated with the severity of the neuronal loss. The electrographic, behavioral, and histological changes induced by b, C, and K fractions were similar to those obtained with other drugs that are commonly used to induce convulsion. The convulsant effects of the crude venom may be caused by the fractions studied in this work.

Behavioral and neurochemical changes induced by aging in dopaminergic systems of male and female rats

Changes induced by aging in dopaminergic activity of male and female rats were compared by behavioral and neurochemical methods. Young (3 months) and old (23 months) rats were used. Aging decreased animal activity in the open field and increased aponiorphine-induced stereotyped behavior. No differences in open field data were observed between males and females. Young and aged female rats had higher striatal DA and HVA levels than males; aging induced a decrease in both striatal DA and HVA levels in males, but not in females. No changes in HVA/DA ratios were observed among the different groups. These results show that aging reduces nigrostriatal activity as well as nigrostriatal DA levels. Furthermore, they indicate that time course events related to aging differ between males and females

Effects of Tityus serrulatus crude venom on the gabaergic and dopaminergic systems of the rat brain

This study was designed to investigate the effect of T. serrulatus scorpion venom on dopamine (DA) and gamma amino butyric acid (GABA) concentrations in different regions of the brain. The ratio of homovanillic acid (HVA) to DA, and the glutamic acid decarboxylase (GAD) activity were determined following intravenous or intracerebral venom injections. The increase in the HYA/DA ratio in the striatum after i.v. or intrastriatal injection could indicate an increase in DA turnover. One hour after i.v. injection of the venom GAD activity was shown to be decreased in the striatum and hypothalamus. After 24 hr GAD activity increased in the striatum and decreased in the hypothalamus and brain stem. These results could indicate different effects of the venom on the GABA system in different areas of the brain. After intrastriatal injection of the scorpion venom, the animals showed stereotyped behavior and rotation activity. Following intrahippocampal injection, myoclonus and orofacial automatisms, which constitute pro-convulsive signals, were observed. These behavioral alterations could be, at least in part, related to the GABA and dopamine alterations caused by the venom, since stereotypy, circling behavior and convulsions are dependent on dopamine and/or GABA.

Behavioural and electroencephalographic effects of Tityus serrulatus scorpion venom in rats

This study was designed to investigate the convulsant effects of T. serrulatus scorpion venom in rats. Pretreatment of rats with venom increased the minimum convulsant dose of picrotoxin, impaired convulsion generalization and displaced to the left the dose-response curve for picrotoxin. It also decreased the intensity but prolonged the duration of seizures caused by pentylenetetrazol injection. Microinjection of the venom into the dorsal hippocampus induced behavioural alterations and epileptiform waves int he EEG. Venom also altered the threshold for, and intensity of, convulsions induced in different experimental models of epilepsy. Different fractions of the venom may be responsible for these different effects. Therefore, purification of venom toxins is necessary for the complete understanding of the present results.